The cholecystokinins (CCK) are a family of peptide amides that are produced by endocrine cells in the gut and by peripheral and central neurons. Although the physiological roles of neural CCK remain to be elucidated, administration of CCK and the related peptide ceruletide causes numerous behavioral effects in laboratory animals. Clinically, these peptides reduced psychotic symptoms in schizophrenics. The profound actions exerted by CCKs and ceruletide suggest that endogenous CCKergic neurons mediate a variety of functions in central systems controlling behavior. Nonetheless, the mechanisms for the pharmacological actions of CCK in behavior remain unclear. Recent interest has focused on the interactions of CCK with dopaminergic systems. In preliminary studies, however, subcutaneously administered CCK octapeptide (CCK-8) potentiated the number of head twitches elicited by the serotonin (5-HT) precursor 5-hydroxy-L-tryptophan (L-5-HTP) in carbidopa-pretreated mice. Current evidence suggests that this motor stimulant action of L-5-HTP is mediated at the 5-HT-2 class of serotonergic receptors and is inhibited by 5-HT antagonists, some adrenergic antagonists and a restricted group of neuroleptic and antidepressant drugs. The proposed studies explore the mechanisms by which peripheral CCK-8 enhances head twitches produced by L-5-HTP in mice by: 1) determining the dose-response curve for this action of CCK-8; 2) assessing the behavioral selectivity of CCK-8 in altering the stimulation by L-5-HTP of head twitches, locomotion and other motor activity; 3) comparing these effects of CCK-8 on motor behavior with those of CCK-4, desulfated CCK-8 and ceruletide; 4) testing whether CCK-8 also enhances head twitches elicited by the 5-HT agonists quipazine and 5-methoxy-N,N-dimethyltryptamine; 5) determining the effects of antagonists of serotonin and CCK receptors on these motor actions of CCK-8; and 6) comparing the effects of CCK-8 and CCK-4, in vitro and ex vivo, on the binding of [3-H]ketanserin, a ligand for 5-HT-2 receptors, to cortical membranes from mice. In concert, these experiments test the hypothesis that peripheral CCK-8 enhances behaviors produced by serotonergic drugs by increasing the number of 5-HT-2 binding sites in the brain. Thus, this investigation will provide new information about mechanisms for the behavioral actions of CCK and may help to elucidate a functional role for the interaction of endogenous CCK with central monoaminergic receptors.